Comparing glutathione peroxidase and glutathione reductase activity and their associations with cardiovascular measures in Africans and Caucasians : the SABPA study

Abstract

Motivation Various factors may contribute to the changing prevalence of cardiovascular disease (CVD) occurring amongst urbanized Black Africans. Changes in eating patterns and exposure to increased levels of oxidants may play a role. Accumulative amounts of data indicate the role that oxidative stress may play in the pathogenesis of hypertension, including changes in vascular tone of resistance arteries and vascular remodelling. The endogenous antioxidant enzymes glutathione peroxidase and glutathione reductase work synergistically to maintain intracellular redox balance. Both these enzymes have been indicated to have varying levels of activities with changes in blood pressure. Furthermore, GPx activity was shown to differ between Caucasians and African-Americans with Africans displaying significantly lower activity of GPx. An ethnic difference in GR activity is yet to be shown. A single study has indicated a negative association between GPx activity and blood pressure. No independent relationships have been established between both enzyme activities and the following cardiovascular measures: systolic and diastolic blood pressure, intima-media thickness and the compliance of arteries. Aims The aims of the study were firstly to compare glutathione peroxidase (GPx) and glutathione reductase (GR) activity between a cohort of African and Caucasian participants. A secondary aim was to explore whether relationships exist between cardiovascular measures such as ambulatory systolic and diastolic blood pressure (SBP and DBP), carotid media thickness (cIMT) and pulse wave velocity (PWV), with these GPx activity and GR activities in both ethnic groups. Method This study forms part of the Sympathetic Activity and ambulatory Blood Pressure in Africans (SABPA) study, which was conducted between the period of February 2008 and May 2009. Four hundred and nine teachers (Africans, n= 200 and Caucasians, n=209) formed part of the multi-disciplinary comparative cohort study and hailed from the Kenneth Kaunda educational district, North West Province, South Africa. All procedures were approved by the ethics committee of the North-West University and conformed to the ethical guidelines of the Declaration of Helsinki. Ambulatory blood pressure measurements were taken from 08h00 to 06h00 the next day and included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR). Urine was collected for a period of eight hours overnight. The participants underwent anthropometric measurements which included: weight and height which were used to calculate body mass index (BMI). Thereafter cardiovascular measurements were performed, that included carotid dorsalis-pedis pulse wave velocity (cdPWV). Carotid intima-media thickness (cIMT) was determined with an ultrasound system and the mean cross-sectional wall area (CSWA) was calculated. Blood samples were taken by a registered nurse to measure fasting glucose levels in sodium fluoride plasma. The following biochemical markers were determined in serum: high sensitivity C-reactive protein (CRP) cotinine (metabolite of nicotine) and gamma glutamyl transferase (GGT). Additionally, albumin and creatinine were measured from urine samples and estimated creatinine clearance (eCrCl) was calculated. Serum peroxides (ROS) and total glutathione (GSH) levels as well as GPx and GR activities were determined. All biochemical measurements with a non-Gaussian spread were logarithmically transformed, including: fasting glucose, CRP, high density lipoprotein (HDL), triglycerides, GR activity, ROS, GGT, and eCrCl. Basic statistical analysis (t-tests and Chi- square tests) were used to depict the characteristics of the study population according to ethnicity. Pearson, partial and multiple regression analyses were used to demonstrate correlations between these two enzymes and cardiovascular variables. Results As the aim of this study was to compare variables between ethnic groups, participants were divided according to ethnicity. Cardiovascular measures, including ambulatory SBP, DBP, MAP, PP and HR, were significantly higher in Africans. This was also true for functional (cdPWV) and structural (cIMT and CSWA) vascular markers. ROS and total GSH levels as well as GR activity were higher, while GPx activity was lower in Africans when compared to Caucasians. Furthermore, cIMT significantly correlated with GR activity in Africans; however, after adjustment for age, gender, BMI, cotinine and GGT it was no longer significant. cdPWV and GR activity as well as eCrCl and GPx were shown to correlate in the Caucasian group. The correlation between cdPWV and GR activity remained significant with the addition of a correlation between cdPWV and GPx activity after were made. Forward stepwise linear regression showed an independent negative association between cdPWV and GPx activity in Caucasians. This remained true even after separate exclusion of subjects using anti-hypertensive medication and/or anti-oxidants as well as HIV-infected subjects. Conclusion Biochemical analyses indicated significant differences in the activity of GPx and GR between Africans and Caucasians. GPx activity was found to be higher and GR activity lower in Caucasians when compared to Africans. The higher activity of GPx is associated with lower cdPWV, indicating a vascular protective effect against arterial stiffening in Caucasians. GPx activity may be lower in Africans due to selenium deficiency or a polymorphism in the GPx gene. In future studies selenium status should be determined to investigate the clinical application of selenium supplementation as a measure to increase GPx activity and subsequently decrease arterial stiffening.